1 DALYs, G. B. D. & Collaborators, H. Global, regional, and national disability-adjusted life-years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE), 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet 388, 1603-1658, doi:10.1016/S0140-6736(16)31460-X (2016).
2 Darveau, R. P. Periodontitis: a polymicrobial disruption of host homeostasis. Nat Rev Microbiol 8, 481-490, doi:10.1038/nrmicro2337 (2010).
3 Ebersole, J. L. et al. Aging, inflammation, immunity and periodontal disease. Periodontol 2000 72, 54-75, doi:10.1111/prd.12135 (2016).
4 Coppe, J. P., Desprez, P. Y., Krtolica, A. & Campisi, J. The senescence-associated secretory phenotype: the dark side of tumor suppression. Annu Rev Pathol 5, 99-118, doi:10.1146/annurev-pathol-121808-102144 (2010).
5 Hayflick, L. The Limited in Vitro Lifetime of Human Diploid Cell Strains. Exp Cell Res 37, 614-636, doi:10.1016/0014-4827(65)90211-9 (1965).
6 Kuilman, T., Michaloglou, C., Mooi, W. J. & Peeper, D. S. The essence of senescence. Genes Dev 24, 2463-2479, doi:10.1101/gad.1971610 (2010).
7 Acosta, J. C. et al. Chemokine signaling via the CXCR2 receptor reinforces senescence. Cell 133, 1006-1018, doi:10.1016/j.cell.2008.03.038 (2008).
8 Kuilman, T. et al. Oncogene-induced senescence relayed by an interleukin-dependent inflammatory network. Cell 133, 1019-1031, doi:10.1016/j.cell.2008.03.039 (2008).
9 Wajapeyee, N., Serra, R. W., Zhu, X., Mahalingam, M. & Green, M. R. Oncogenic BRAF induces senescence and apoptosis through pathways mediated by the secreted protein IGFBP7. Cell 132, 363-374, doi:10.1016/j.cell.2007.12.032 (2008).
10 Watanabe, S., Kawamoto, S., Ohtani, N. & Hara, E. Impact of senescence-associated secretory phenotype and its potential as a therapeutic target for senescence-associated diseases. Cancer Sci 108, 563-569, doi:10.1111/cas.13184 (2017).
11 Hsu, T. N. et al. Targeting FAT1 Inhibits Carcinogenesis, Induces Oxidative Stress and Enhances Cisplatin Sensitivity through Deregulation of LRP5/WNT2/GSS Signaling Axis in Oral Squamous Cell Carcinoma. Cancers (Basel) 11, doi:10.3390/cancers11121883 (2019).
12 Kiyoshima, T. et al. Oxidative stress caused by a low concentration of hydrogen peroxide induces senescence-like changes in mouse gingival fibroblasts. Int J Mol Med 30, 1007-1012, doi:10.3892/ijmm.2012.1102 (2012).
13 Yamada, K., Matsushita, K., Wang, J. & Kanekura, T. Topical Glucose Induces Claudin-1 and Filaggrin Expression in a Mouse Model of Atopic Dermatitis and in Keratinocyte Culture, Exerting Anti-inflammatory Effects by Repairing Skin Barrier Function. Acta Derm Venereol 98, 19-25, doi:10.2340/00015555-2807 (2018).
14 Iwayama, T. et al. Adiponectin regulates functions of gingival fibroblasts and periodontal ligament cells. J Periodontal Res 47, 563-571, doi:10.1111/j.1600-0765.2012.01467.x (2012).
15 Yi, Z. et al. Effects of Nonsteroidal Anti-inflammatory Drugs on the Self-renewal Capacity of Blast Progenitors in Hematological Malignancies. Anticancer Res 37, 2315-2322, doi:10.21873/anticanres.11569 (2017).
16 Rodier, F. & Campisi, J. Four faces of cellular senescence. J Cell Biol 192, 547-556, doi:10.1083/jcb.201009094 (2011).
17 Yang, J. et al. Enhanced activity of macrophage M1/M2 phenotypes in periodontitis. Arch Oral Biol 96, 234-242, doi:10.1016/j.archoralbio.2017.03.006 (2018).
18 Ferencz, B. & Gerritsen, L. Genetics and underlying pathology of dementia. Neuropsychol Rev 25, 113-124, doi:10.1007/s11065-014-9276-3 (2015).
19 Genco, R. J. & Borgnakke, W. S. Risk factors for periodontal disease. Periodontol 2000 62, 59-94, doi:10.1111/j.1600-0757.2012.00457.x (2013).
20 Van der Velden, U. Effect of age on the periodontium. J Clin Periodontol 11, 281-294, doi:10.1111/j.1600-051x.1984.tb01325.x (1984).
21 van der Velden, U. The onset age of periodontal destruction. J Clin Periodontol 18, 380-383, doi:10.1111/j.1600-051x.1991.tb02304.x (1991).
22 Tsalikis, L. The effect of age on the gingival crevicular fluid composition during experimental gingivitis. A pilot study. Open Dent J 4, 13-26, doi:10.2174/1874210601004010013 (2010).
23 Ovadya, Y. et al. Impaired immune surveillance accelerates accumulation of senescent cells and aging. Nat Commun 9, 5435, doi:10.1038/s41467-018-07825-3 (2018).
24 Baker, D. J. et al. Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature 479, 232-236, doi:10.1038/nature10600 (2011).
25 Baker, D. J. et al. Naturally occurring p16(Ink4a)-positive cells shorten healthy lifespan. Nature 530, 184-189, doi:10.1038/nature16932 (2016).
26 Chen, L. et al. 1,25-Dihydroxyvitamin D exerts an antiaging role by activation of Nrf2-antioxidant signaling and inactivation of p16/p53-senescence signaling. Aging Cell 18, e12951, doi:10.1111/acel.12951 (2019).
27 Macip, S. et al. Inhibition of p21-mediated ROS accumulation can rescue p21-induced senescence. EMBO J 21, 2180-2188, doi:10.1093/emboj/21.9.2180 (2002).
28 Tabasso, A. F. S., Jones, D. J. L., Jones, G. D. D. & Macip, S. Radiotherapy-Induced Senescence and its Effects on Responses to Treatment. Clin Oncol (R Coll Radiol) 31, 283-289, doi:10.1016/j.clon.2019.02.003 (2019).
29 Damgaard, C. et al. Porphyromonas gingivalis-induced production of reactive oxygen species, tumor necrosis factor-alpha, interleukin-6, CXCL8 and CCL2 by neutrophils from localized aggressive periodontitis and healthy donors: modulating actions of red blood cells and resolvin E1. J Periodontal Res 52, 246-254, doi:10.1111/jre.12388 (2017).
30 He, S. & Sharpless, N. E. Senescence in Health and Disease. Cell 169, 1000-1011, doi:10.1016/j.cell.2017.05.015 (2017).
31 Sorsa, T., Tjaderhane, L. & Salo, T. Matrix metalloproteinases (MMPs) in oral diseases. Oral Dis 10, 311-318, doi:10.1111/j.1601-0825.2004.01038.x (2004).
32 Sica, A. & Mantovani, A. Macrophage plasticity and polarization: in vivo veritas. J Clin Invest 122, 787-795, doi:10.1172/JCI59643 (2012).
33 Matjusaitis, M., Chin, G., Sarnoski, E. A. & Stolzing, A. Biomarkers to identify and isolate senescent cells. Ageing Res Rev 29, 1-12, doi:10.1016/j.arr.2016.05.003 (2016).
34 Bussian, T. J. et al. Clearance of senescent glial cells prevents tau-dependent pathology and cognitive decline. Nature 562, 578-582, doi:10.1038/s41586-018-0543-y (2018).
35 Kovacovicova, K. et al. Senolytic Cocktail Dasatinib+Quercetin (D+Q) Does Not Enhance the Efficacy of Senescence-Inducing Chemotherapy in Liver Cancer. Front Oncol 8, 459, doi:10.3389/fonc.2018.00459 (2018).
36 Zhang, P. et al. Senolytic therapy alleviates Abeta-associated oligodendrocyte progenitor cell senescence and cognitive deficits in an Alzheimer's disease model. Nat Neurosci 22, 719-728, doi:10.1038/s41593-019-0372-9 (2019).
37 Zhu, Y. et al. The Achilles' heel of senescent cells: from transcriptome to senolytic drugs. Aging Cell 14, 644-658, doi:10.1111/acel.12344 (2015).
38 Kirkland, J. L., Tchkonia, T., Zhu, Y., Niedernhofer, L. J. & Robbins, P. D. The Clinical Potential of Senolytic Drugs. J Am Geriatr Soc 65, 2297-2301, doi:10.1111/jgs.14969 (2017).
39 Chang, J. et al. Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice. Nat Med 22, 78-83, doi:10.1038/nm.4010 (2016).